The Clinical Molecular Profiling Core (CMPC) is a collaborative core that seeks to go beyond the common service paradigm of other cores. The expertise of the personnel allows involvement from the start of a project, such as the protocol development, though performance of the assay and biostatistical analyses. Currently, our main function is to support clinical trials at the National Cancer Institute (NCI) and to that end we have collaborations with many of the branches in the Center for Cancer Research (CCR), NCI and beyond within the NIH. The status of these collaborations range from preliminary discussions through protocol development, accrual and analysis, and completion to publication; for those that are completed, we look forward to being involved in follow up studies. Many of the studies are clinical trials testing or identifying drugs for early phase clinical trials. These include studies such as: Molecular profiling and targeted therapy for advanced thoracic malignancies: a biomarker-derived, multiarm, multihistology phase II basket trial Functionally defined therapeutic targets in diffuse intrinsic pontine glioma However, other investigations are more focused on understanding the underlying pathology of specific diseases and are not directly testing a therapy. In the last year these studies included publications on: Genetic and epigenetic analysis of monozygotic twins discordant for testicular cancer Recurrent epimutation of SDHC in gastrointestinal stromal tumors Mutations of epigenetic regulatory genes are common in thymic carcinomas Discovery and validation of methylation markers for endometrial cancer An integrated prognostic classifier for stage I lung adenocarcinoma based on mRNA, microRNA, and DNA methylation biomarkers Characterization of genomic alterations in radiation-associated breast cancer among childhood cancer survivors, using comparative genomic hybridization (CGH) arrays. Significantly, resources have begun to be devoted to actualizing clinical exome sequencing using Illumina next-generation sequencers. To support these studies, the CMPC has expertise in many molecular technologies for the analysis of DNA and RNA from human specimens. State of the art assays found on a wide range of advanced platforms include: DNA sequencing (Sanger and next-generation sequencing), mRNA expression analysis (microarray, real-time PCR, bead-based), epigenomic methylation (microarray and pyrosequencing), array comparative genomic hybridization (microarray), and telomere length assays. Importantly, the CMPC provides full bioinformatics support for all these assays.

Agency
National Institute of Health (NIH)
Institute
National Cancer Institute (NCI)
Type
Scientific Cores Intramural Research (ZIC)
Project #
1ZICBC011040-08
Application #
9154310
Study Section
Project Start
Project End
Budget Start
Budget End
Support Year
8
Fiscal Year
2015
Total Cost
Indirect Cost
Name
Basic Sciences
Department
Type
DUNS #
City
State
Country
Zip Code
Grasso, Catherine S; Tang, Yujie; Truffaux, Nathalene et al. (2015) Functionally defined therapeutic targets in diffuse intrinsic pontine glioma. Nat Med 21:827
Yang, Xiaohong R; Killian, J Keith; Hammond, Sue et al. (2015) Characterization of genomic alterations in radiation-associated breast cancer among childhood cancer survivors, using comparative genomic hybridization (CGH) arrays. PLoS One 10:e0116078
Howard, Brandi; Wang, Yonghong; Xekouki, Paraskevi et al. (2014) Integrated analysis of genome-wide methylation and gene expression shows epigenetic regulation of CYP11B2 in aldosteronomas. J Clin Endocrinol Metab 99:E536-43
Petrini, Iacopo; Meltzer, Paul S; Kim, In-Kyu et al. (2014) A specific missense mutation in GTF2I occurs at high frequency in thymic epithelial tumors. Nat Genet 46:844-9
Waterfall, Joshua J; Killian, J Keith; Meltzer, Paul S (2014) The role of mutation of metabolism-related genes in genomic hypermethylation. Biochem Biophys Res Commun 455:16-23
Azad, Nilofer; Yu, Minshu; Davidson, Ben et al. (2013) Translational predictive biomarker analysis of the phase 1b sorafenib and bevacizumab study expansion cohort. Mol Cell Proteomics 12:1621-31
Aung, Phyu P; Killian, Keith; Poropatich, Carrie O et al. (2013) Primary neuroendocrine tumors of the kidney: morphological and molecular alterations of an uncommon malignancy. Hum Pathol 44:873-80
Miettinen, Markku; Killian, Jonathan Keith; Wang, Zeng-Feng et al. (2013) Immunohistochemical loss of succinate dehydrogenase subunit A (SDHA) in gastrointestinal stromal tumors (GISTs) signals SDHA germline mutation. Am J Surg Pathol 37:234-40
Abaan, Ogan D; Polley, Eric C; Davis, Sean R et al. (2013) The exomes of the NCI-60 panel: a genomic resource for cancer biology and systems pharmacology. Cancer Res 73:4372-82
Di, Li-Jun; Byun, Jung S; Wong, Madeline M et al. (2013) Genome-wide profiles of CtBP link metabolism with genome stability and epithelial reprogramming in breast cancer. Nat Commun 4:1449

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